DRUG-EXPOSURE LIMITATIONS OF ORAL METHOTREXATE AT DOSES GREATER THAN OR
`EQUAL TO 15 MG MAY BE OVERCOME WITH SUBCUTANEOUS ADMINISTRATION
`
`ANTARES PHARMA ANNOUNCES THE PUBLICATION OF A HEAD-TO-HEAD, RANDOMIZED,
`CROSSOVER STUDY OF ORAL VERSUS SUBCUTANEOUS METHOTREXATE IN PATIENTS
`WITH RHEUMATOID ARTHRITIS
`
`
`
`EWING, NJ, April 17, 2014 -- Antares Pharma, Inc. (NASDAQ: ATRS) today announced that the
`Annals of the Rheumatic Diseases has published results from an open-label, head-to-head
`randomized, crossover study comparing the relative bioavailability, safety and tolerability of
`OTREXUP™ to oral methotrexate (MTX) in adult patients with rheumatoid arthritis (RA).
`
`In this multicenter, three-way crossover study, patients greater than or equal to 18 years old with
`adult RA undergoing treatment with MTX for three months or more were assigned to receive one of
`four dose levels of OTREXUP™, 10 mg, 15 mg, 20 mg, and 25 mg weekly in a random sequence of
`three treatments: oral, subcutaneous into the abdomen and subcutaneous into the thigh. For 24
`hours after the administration of each treatment, blood samples were collected to measure drug
`levels and injection sites were assessed. Forty-seven patients completed the study and the results
`showed that the systemic availability of methotrexate following oral dosing plateaus at 15 mg and
`greater. Following administration of OTREXUP™, the systemic availability increased proportionally
`at every dose, which extended the range of exposure compared to patients receiving oral therapy.
`No unexpected adverse events were noted for either formulation in this short term study and higher
`systemic MTX exposure was not associated with increases in adverse events.
`
`“The study results show for the first time that plasma levels of oral dosed MTX are no greater for 20
`mg or 25 mg doses than for 15 mg doses”, said Michael H. Schiff, M.D., Clinical Professor of
`Medicine in the Rheumatology Division at the University of Colorado School Of Medicine in Denver.
`“If a patient fails to respond to 15 mg of MTX orally, it may be more effective to switch to a
`subcutaneous regimen rather than continue to raise the oral dose. These findings may have
`implications on future prescribing habits of specialists”.
`
`Historically, parenteral MTX use has been limited in clinical practice for several reasons including the
`inconvenience of weekly injections by a healthcare professional, and/or the challenges associated
`with teaching patients with impaired hand function, safe, sterile and precise self-injection techniques.
`To address these issues, an easy to use, single-use MTX auto injector (OTREXUP™) was
`developed to optimize the clinical benefit of MTX, potentially leading to cost effective treatment
`outcomes.
`
`Paul K. Wotton, Ph.D., President and Chief Executive Officer, stated, “The publication of this data by
`the Annals of the Rheumatic Diseases adds further validation to the value proposition of OTREXUP.”
`He continued, “The parenteral administration of methotrexate is an accepted treatment method for
`extending the use to higher doses. We believe OTREXUP provides not only greater bioavailability,
`but more precise, hygienic and greater dosing flexibility for RA patients”.
`
`
`The article can be accessed using the following link: http://ard.bmj.com/cgi/content/full/annrheumdis-
`2014-205228
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`IMPORTANT SAFETY INFORMATION (ABBREVIATED)
`
`Otrexup™ (methotrexate) injection, for subcutaneous use
`
`Otrexup can cause serious side effects that can lead to death, including:
` An increased risk of death from organ toxicity. Types of organ toxicity can include:
`gastrointestinal, bone marrow, liver, immune system, nerve, lung, kidneys and skin.
`
` Women who are pregnant are at increased risk for death of the baby and birth defects.
`Women who are pregnant or who plan to become pregnant must not take Otrexup.
`Contraception should be used by both females and males while taking Otrexup. For males,
`pregnancy should be avoided for a minimum of 3 months after treatment with Otrexup, and
`for females, for at least 1 menstrual cycle after treatment.
`
`
`Do not take Otrexup if you:
` Are pregnant or planning to become pregnant
`
` Are breastfeeding
`
` Have alcohol problems
`
` Have liver problems
`
` Have problems fighting infection
`
` Have a blood disorder
`
` Have an allergy to methotrexate
`
`
`Possible side effects of Otrexup
` Fertility problems
` Certain cancers
` Tissue and bone problems
`
`
`Common side effects of Otrexup include: nausea, stomach pain, indigestion, mouth sores, and rash.
`
`You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
`www.fda.gov/medwatch, or call 1-800-FDA-1088. For more information, go to www.Otrexup.com or
`call 1-855-OTREXUP (1-855-687-3987).
`
`About Vibex® Auto Injectors
`
`The Vibex® Auto Injector is a single-dose, disposable pressure assisted auto injector designed to
`provide a fast, safe and time-efficient method of self-injection. The Vibex® system features a
`triggering collar that shields the needle from view. The patented retracting collar springs back and
`locks in place as a protective needle guard after the injection, making the device safe for general
`disposal. Encompassing a wide variety of sizes and designs, this technology operates by using
`pressure to force the drug, solution or suspension through the skin and deposit the drug into the
`subcutaneous tissue. Our proprietary Vibex® disposable auto injector systems combine a low-
`energy, spring-based power source with a shielded needle designed to deliver the needed drug
`solution. Vibex® Auto Injectors are designed, developed and manufactured in America.
`
`About Antares Pharma
`
`Antares Pharma focuses on self-administered parenteral pharmaceutical products. The Company
`has received marketing approval from the U.S. Food and Drug Administration for OTREXUP™
`(methotrexate) injection for the treatment of adults with severe active rheumatoid arthritis, children
`with active polyarticular juvenile idiopathic arthritis and adults with severe recalcitrant psoriasis.
`Antares Pharma is also developing VIBEX® QS T for testosterone replacement therapy. The
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`Company's technology platforms include VIBEX® disposable Medi-Jet, disposable multi-use pen
`injectors marketed as Tjet® and Zomajet® by Teva
`injectors and reusable needle-free
`Pharmaceutical Industries, Ltd (Teva) and Ferring Pharmaceuticals (Ferring), respectively. Antares
`Pharma has a multi-product deal with Teva that includes Tev-Tropin® [somatropin (rDNA origin) for
`injection] human growth hormone (hGH), VIBEX® epinephrine and several other products. Antares
`Pharma’s partnership with Ferring includes Zomacton® hGH (somatropin) injection. In the U.S.
`Antares has received FDA approval for Gelnique 3%™ (oxybutynin) gel, a treatment for overactive
`bladder that is marketed by Actavis. Elestrin® (estradiol gel) is FDA approved for the treatment of
`moderate-to-severe vasomotor symptoms associated with menopause, and is marketed in the U.S.
`by Meda Pharma. Antares Pharma has two facilities in the U.S. The Parenteral Products Group
`located in Minneapolis, Minnesota directs the manufacturing and marketing of the Company’s
`reusable needle-free injection devices and related disposables, and develops its disposable
`pressure-assisted Medi-Jet and pen injector systems. The Company’s corporate office and Product
`Development and Commercial Groups are located in Ewing, New Jersey.
`
`Safe Harbor Statement
`
`This press release contains forward-looking statements within the meaning of the safe harbor
`provisions of the Private Securities Litigation Reform Act of 1995. These statements are indicated by
`the words “may,” “will,” “plans,” “intends,” “believes,” “expects,” “anticipates,” “potential,” “could,”
`“would,” “should,” and similar expressions. Such forward-looking statements are not guarantees of
`future performance and are subject to risks and uncertainties that may cause actual results to differ
`materially from those anticipated by the forward-looking statements. These risks and uncertainties
`include, among others, changes in revenue growth and difficulties or delays in the initiation,
`progress, or completion of product development. Additional information concerning these and other
`factors that may cause actual results to differ materially from those anticipated in the forward-looking
`statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K
`for the year ended December 31, 2013, and in the Company's other periodic reports and filings with
`the Securities and Exchange Commission. The Company cautions investors not to place undue
`reliance on the forward-looking statements contained in this press release. All forward-looking
`statements are based on information currently available to the Company on the date hereof, and the
`Company undertakes no obligation to revise or update these forward-looking statements to reflect
`events or circumstances after the date of this press release, except as required by law.
`
`
`
`Contacts:
`Jack Howarth
`Vice President, Corporate Affairs
`609-359-3016
`jhowarth@antarespharma.com
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